Table 3.

Molecular findings in CNTNAP2

CNTNAP2	Defect	Array Platform and details of NRXN1/CNTNAP2 deletion	Validation of Array data	Inheritance	Carrier parent	Other non-polymorphic CNVs	NRXN1 sequencing	CNTNAP2 sequencing
C1	CNTNAP2 c.1175_1176dup; p.D393RfsX51	Affymetrix 6.0 SNP Array, normal results for CNTNAP2 and NRXN1		paternal	healthy	chr9:9.337.920-10.207.671 mat dup chr13:19.104.340-19.477.398 mat dup	normal	no 2nd mutation; MLPA normal
C2	CNTNAP2 c.2153G>A, p.W718X	Affymetrix 6.0 SNP Array, normal results for CNTNAP2 and NRXN1		not known	not known	none	normal	no 2nd mutation; MLPA normal
C3	CNTNAP2 c.1083G>A, splice site (p.V361V)	Affymetrix 500 K SNP Array, normal results for CNTNAP2 and NRXN1		paternal	healthy	none	normal	no 2nd mutation; MLPA normal
C4	CNTNAP2 c.1083G>A, splice site (p.V361V)	Illumina 317 K SNP Array, normal results for CNTNAP2 and NRXN1		maternal	healthy	pathogenic frameshift mutation in MEF2C (P7, Zweier et al. 2010) [28]	normal	no 2nd mutation; MLPA normal
C5	CNTNAP2 deletion of exons 2-3	Affymetrix 6.0 SNP Array chr7:146.079.333-146.194.785 115 kb (69 array marker)	Affymetrix 6.0 SNP Array of the parents	maternal	healthy	none	normal, one silent variant	no 2nd mutation
C6	CNTNAP2 deletion of exons 3-4	Illumina Human 660W-Quad chr7:146.144.267-146.374.539 230 kb (53 array marker)	qPCR as reported previously [32]	maternal	healthy	none	normal	no 2nd mutation
C7	CNTNAP2 deletion of exons 21-24	Agilent 2 × 400 K chr7:147.702.165-148.378.711 677 kb	customized Oligonucleotide array	de novo	healthy	chr7:92.394.428-92.530.356 del chr7:93.464.449-94.430.690 del, both de novo conventional karyotyping: 46,XX,der(4)t(4;10)(q25;q24), der(7)t(4;7)(q25;q32), der(10)inv(10)(p13q24)(7;10)(q32;p13), de novo	normal	no 2nd mutation
published biallelic defects n = 13[24,25]	2x CNTNAP2 deletion of exons 2-9, homozygous [26]; 1x CNTNAP2 deletion of exons 5-8 + IVS10-1G>T [26]; 10x CNTNAP2 c.3709delG, homozygous [24,25]	2x Affymetrix 500 K/250 K Nsp SNP Array; 1x Affymetrix 6.0 SNP Array [26]; 10x no		parents heterozygous carriers
published heterozygous defects n = 12 [1,3,7,12,21,33]	2x translocation disrupting CNTNAP2 [12,33], 1x inversion disrupting CNTNAP2 [3], 5x CNTNAP2 deletion [1,7,21], 4x missense variant in CNTNAP2 [3]	3x BAC array [7], 1x NimbleGen custom array [21], 220 kb-11 Mb		2x not reported [7], 4x inherited [3], 2x paternal [1,21], 2x de novo [3,7] 2x balanced in parent (translocation) [12,33]

mat, maternal; pat, paternal; dup, duplication; del, deletion; ass., associated; qPCR, quantitative Real-Time-PCR; non-polymorphic CNVs: CNVs that have not been reported in the Toronto Database of Genome Variants or have not been identified in one of our molecularly karyotyped healthy control indivuals